Table of Contents

Volume 6, Issue 9

  September 2010

  Pages 683 - 768

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Riedmann
Page 683
http://dx.doi.org/10.4161/hv.6.9.13485
Abstract | PDF







NEWS, POLICY AND PROFILES

Open Access Article

News

Eva Riedmann
Pages 684 - 688
http://dx.doi.org/10.4161/hv.6.9.13541
Abstract | PDF

HPV vaccine protects against pre-cancerous growths;
One vaccine for a range of cancers;
Pertussis outbreak in California;
Vaccine to combat chronic stress;
Seasonal flu vaccines on the way;
Computer-aided design of live viral vaccine;
HIV vaccine research: Hope for renaissance;
2010 Albert B. Sabin Gold Medal Award



Open Access Article

Questions for Biotechs: Genocea Biosciences

Jessica Flechtner
Pages 684 - 688
http://dx.doi.org/10.4161/hv.6.9.13542
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

Price as a double-edged sword in the golden era of vaccines

Matthew M. Davis
Pages 689 - 693
http://dx.doi.org/10.4161/hv.6.9.13496
PDF




BOOK REVIEW

Open Access Article

Plant-produced microbial vaccines: Alexander V. Karasev, editor
Current topics in microbiology and immunology 2009; v. 332

Vidadi Yusibov and Stephen J. Streatfield
Pages 694 - 695
http://dx.doi.org/10.4161/hv.6.9.12006
Abstract | PDF







PRODUCT REVIEW

Open Access Article

Development of sanofi pasteur tetravalent dengue vaccine

Bruno Guy, Melanie Saville and Jean Lang
Pages 696 - 705
http://dx.doi.org/10.4161/hv.6.9.12739
Abstract | PDF

The sanofi pasteur tetravalent dengue vaccine candidate is composed of 4 recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes. Pre-clinical studies have demonstrated that the TV dengue vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies also showed that the TV dengue vaccine induced controlled stimulation in human dendritic cells, and significant immune responses in monkeys. TV dengue vaccine reactogenicity, viraemia induction and antibody responses were investigated in three Phase I trials in the USA, the Philippines and Mexico, in a two or three-dose regimen over a 12 month period. Results showed that the majority of adverse events were mild to moderate and transient in nature. Viraemia was transient and low, and was not increased after initial dengue TV administration, even in the case of incomplete responses. Seropositivity [≥ 10 in a PRNT 50 assay] was 100% for all four serotypes in flavivirus-naive adults injected with 3 doses of TV dengue vaccine in the USA. Similarly, seropositivity was 88–100% following three administrations in flavivirus-naive Mexican children aged 2–5 years. Furthermore, the proportion of seropositive subjects increased with each dengue TV injection in the Philippines where baseline flavivirus immunity was high. Responses were also monitored at the cellular level in humans, and their level and nature were in good agreement with the observed safety and the immunogenicity of the vaccine. Finally, the challenges inherent to the development of such TV dengue vaccines will also be discussed in the last part of this review. In conclusion, preclinical and clinical results support the favorable immunogenicity and short-term safety of the dengue TV vaccine. An extensive clinical development program for dengue TV is underway including completion of the enrollment of 4000 4-11 years old children in an efficacy trial in Thailand, in an area of high dengue incidence. Assuming continued successful outcomes, initial submissions to regulatory authorities are envisaged within a 5-year period.




REVIEWS

Open Access Article

Recent advances in the development of novel mucosal adjuvants and antigen delivery systems

Wangxue Chen, Girishchandra B. Patel, Hongbin Yan and Jianbing Zhang
Pages 706 - 714
http://dx.doi.org/10.4161/hv.6.9.11561
Abstract | PDF

Mucosal infections and associated diseases remain a major socio-economic burden to society. Since parenteral immunizations fail to induce efficient protective immunity at mucosal surfaces, mucosal immunization is a logical approach to prevent and treat mucosally-initiated infections. All currently approved human mucosal vaccines are based on attenuated or killed whole pathogen cells but this strategy does pose safety concerns. Therefore, substantial effort is being invested to develop safe and effective mucosal adjuvants and delivery systems for mucosal vaccines. Encouragingly, some of these have progressed to advanced preclinical and clinical studies. This review discusses the promising preclinical research and the potential applications of several novel mucosal adjuvants and delivery systems: an archaeal lipid mucosal vaccine adjuvant and delivery (AMVAD) system, 3’,5’-cyclic diguanylic acid (c-di-GMP) and detoxified bacterial AB5 toxins. The potential and challenges in targeting M cells for mucosal vaccination are also discussed.

Open Access Article

HPV vaccine acceptance, utilization and expected impacts in the US: Where are we now?

Amanda F. Dempsey and Divya A. Patel
Pages 715 - 720
http://dx.doi.org/10.4161/hv.6.9.12730
Abstract | PDF

Human papillomavirus (HPV) vaccines represent a remarkable opportunity for the primary prevention of cervical cancer and other HPV-related diseases. With almost four years of vaccine availability now accrued in the United States (US.), data are beginning to accumulate about vaccine utilization patterns and how these may be affected by public opinions about the vaccines. This article describes the burden of HPV infection and related disease in the US, and reviews what is currently known about HPV vaccine utilization among adolescent and young adult females in this country. In addition, we report on emerging data on the personal and attitudinal factors that appear to influence HPV vaccine utilization and discuss how these data may be useful for designing future interventions to improve uptake of these vaccines. Finally, we re-examine cost-effectiveness studies of HPV vaccines, taking into account updated information on utilization of, and public attitudes about, these vaccines.




RESEARCH PAPERS

Open Access Article

Immunogenicity, safety and tolerance of a purified duck embryo vaccine (PDEV, VAXIRAB) for rabies post-exposure prophylaxis: Results of a multicentric study in India

Bangalore Jayakrishna Mahendra , Shampur Narayan Madhusudana , Gadey Sampath, Soma Subhra Datta, Doddabele Hanumanthaiah Ashwathnarayana, Gonibeedu Manjunath Venkatesh, Mysore Kalappa Sudarshan, Gangaboraiah Bilugumba and Manjula Shamanna
Pages 721 - 724
http://dx.doi.org/10.4161/hv.6.9.12216
Abstract | PDF

Rabies continues to be a major public health problem in India. Nearly 17 million people are getting exposed to this disease every year. Therefore the need for effective post-exposure prophylaxis with safe and potent modern rabies vaccines continues to exist. Purified Duck Embryo Vaccine (PDEV) was introduced in this country to meet the ever increasing need for modern rabies vaccines. In this study we have assessed the safety, imunogenicity and tolerance of an indigenously manufactured PDEV in people exposed to dog and other animal bites. One hundred and fifty people (5-59 years) who were having WHO category II or III animal bites were vaccinated with PDEV using the Essen Intramuscular regimen and rabies immunoglobluin (RIG) was administered to category III exposures.. Their blood samples were analyzed for rabies virus neutralizing antibody response (RVNA) by Rapid Fluorescent Focus Inhibition Test (RFFIT) on day 0, 14, 30, 90, 180 and 365. Adverse effects to vaccines were monitored during the course of vaccination. There was 100% sero- conversion from day 14 onwards with adequate RVNA titers ( >= 0.5 IU/mL) up to day 365. The incidence of side effects was minimal and self limiting. Hence it can be concluded that indigenously manufactured PDEV (Vaxirab) is a safe and immunogenic vaccine and can safely be used for post-exposure prophylaxis.

Open Access Article

Successful hepatitis B immunization in non- and low responding health care workers

Ulrich Heininger, Muriel Gambon, Verena Gruber and Daniela Margelli
Pages 725 - 728
http://dx.doi.org/10.4161/hv.6.9.12420
Abstract | PDF

Health care workers (HCW) are at increased risk for acquisition of hepatitis B virus (HBV) infection from occupational exposure. This can be prevented by active immunization. We performed a retrospective chart review of HCW who were persistent low (anti-HBs antibody values <100 U/L) or non responders (<10 U/L) after 6 active immunizations and demonstrate successful immunization (anti-HBs >100 U/l) after a total of 8-14 vaccine doses in 13 such HCW by use of various vaccination schedules. This “proof of principle” should encourage occupational health care providers to convince HCW to accept further vaccine doses until the targeted threshold considered to be the correlate of immunity has been reached. Prospective studies should be performed to determine the optimal schedule of further booster doses for HCW who are persistent non or low responders.

Open Access Article

Vaccine effectiveness against laboratory-confirmed influenza in infants: A matched case control study

Lauren W. Cochran, Steven Black, Nicola P. Klein, Cornelia L. Dekker, Edwin Lewis and Arthur L. Reingold
Pages 729 - 735
http://dx.doi.org/10.4161/hv.6.9.12470
Abstract | PDF

Influenza is a common and potentially serious infection in infants. Previous studies of influenza vaccine in this age group have reported widely varying estimates of vaccine effectiveness, and few have used laboratory confirmation of influenza diagnoses. We evaluated the effectiveness of 1 and 2 doses of the trivalent inactivated vaccine against laboratory-confirmed influenza in children aged 6 to 23 months within the Kaiser Permanente Northern California Medical Care Program for the 2003-2004, 2004-2005, and 2005-2006 influenza seasons. 1648 children were included in the analyses, with an average of 4.5 controls matched to each of the 300 cases (213, 29, and 58 cases identified for each of the influenza seasons, respectively) based on birth month/year and zip code. Vaccination status was determined as of 14 days prior to the case patient’s positive test result. Conditional logistic regression was used to calculate vaccine effectiveness for each season, adjusting for chronic medical conditions and other possible confounders. During the 2005-2006 influenza season, when predominant circulating virus strains and vaccine strains were well matched, vaccination was 76% [95% CI: 37-91%] effective against laboratory-confirmed infection. There was no statistically significant effect of vaccination, however, for the 2003-2004 or 2004-2005 seasons. Our results highlight the need for further study of influenza vaccine effectiveness in this age group.

Open Access Article

Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: Results from a controlled study in metastatic breast cancer patients.

Vladimir Mulens, Ana de la Torre , Patricia Marinello, Ronald Rodríguez, Jorge Cardoso, René Díaz, Miguel O´Farrill, Amparo Macias, Carmen Viada, Giselle Saurez, Adriana Carr, Tania Crombet, Zaima Mazorra, Rolando Perez and Luis E. Fernández
Pages 736 - 744
http://dx.doi.org/10.4161/hv.6.9.12571
Abstract | PDF

Increased levels of NeuGc-containing gangliosides have been described in human breast cancer. A controlled Phase II clinical trial was conducted in patients with metastatic breast cancer to evaluate immunogenicity, safety and to identify evidences of biological activity of a cancer vaccine composed by NeuGcGM3 in a proteoliposome of Neisseria meningitidis together with Montanide ISA 51 as adjuvant. After first line chemotherapy, 79 women were randomized 1:1 to receive the vaccine candidate or best supportive care. All patients achieved at least stable disease to the first line therapy for the metastatic condition. Treatment consisted on 5 vaccine doses every 2 weeks and then, monthly re-immunization to complete 15 doses. Vaccination with the NeuGcGM3 based vaccine was safe and the most frequent adverse events consisted on injection site reactions, fever, arthralgia and chills. The vaccine was immunogenic and a sustained increase of both IgG and IgM antibody titters against NGcGM3 was observed after the second vaccination month. Antibodies were able to recognize the NeuGcGM3⁺ murine tumor cell line L1210 and the myeloma cell line P3X63. Humoral response was specific since vaccination did not result in Neu-Acetyl GM3 or GM2-antibody response. Hyperimmune sera from vaccinated patients were able to prevent the NeuGcGM3 mediated CD4 down-modulation on T lymphocytes. In the intent to treat analysis, there was a trend toward a survival advantage for the vaccine group and this effect was significant for women bearing non-visceral metastasis. Two phase III clinical studies with this vaccine candidate are ongoing.

Open Access Article

Forecasting dengue vaccine demand in disease endemic and non-endemic countries

Ananda Amarasinghe, Ole Wichmann, Harold S. Margolis and Richard T. Mahoney
Pages 745 - 753
http://dx.doi.org/10.4161/hv.6.9.12587
Abstract | PDF

Background: A dengue vaccine in large-scale clinical trials could be licensed in several years. We estimated the potential vaccine demand for different introduction strategies in 54 dengue-endemic countries and for travelers from non-endemic countries to enable vaccine producers and public health agencies to better prepare for timely utilization of the vaccine.

Results: Under Our assumptions, 2.4-3.5 billion dengue vaccine doses would be needed in the first five years after introduction with >75% delivered in the public sector. Among 20 potential ‘early-adopter’ countries, an estimated 0.9-1.4 billion doses would be needed for the same introduction approach. For the private sector, covering 10% of children and 30% of adults an estimated 443-664 million doses would be required. In non-endemic countries, travelers could use an estimated 59-89 million vaccine doses, although the present product profile would make it unlikely to be able to administer vaccine in a timely manner

Methods: Calculations were based on 2015-2020 population projections for endemic countries in Asia and the Americas with populations >100.000. For dengue-endemic countries we assumed country-wide routine 12-23 month-old vaccination and catch-up vaccination among 2-14 year-old children employing a 2 or 3-dose schedule. Assumptions on expected vaccination coverage were based on country-specific public, private, and travelers’ sectors immunization performance.

Conclusions: Our results project an upper-limit estimate of vaccine demand, with actual demand depending on country priorities, cost and product profile. Given the potential for a dengue vaccine, policymakers in endemic and non-endemic countries should consider appropriate implementation strategies in advance of licensure.




COMMENTARIES

Open Access Article

Public health measures & individualized decision-making: The confluence of H1N1 vaccine and Islamic bioethics

Aasim I. Padela
Pages 754 - 756
http://dx.doi.org/10.4161/hv.6.9.12015
Abstract | PDF

Vaccinations are amongst the most cost-effective and successful public health interventions. During the H1N1 influenza pandemic public health organizations around the world mobilized to procure and deliver vaccinations to the at-risk populations in order to reduce spread of, and decrease morbidity and mortality from, the swine flu. With the focus on delivering vaccines at a population-level, state and national governmental agencies coordinated to procure vaccine supplies within the United States. However all healthcare decisions trickle down to the individual level. In this essay I narrate the tensions and challenges I faced to make decisions for myself and my family on whether we should get the H1N1 vaccines, while being true to both religious values and the medical science. At the end of the narration I reflect on ethical and policy questions we must address during public health vaccination efforts.

Open Access Article

Malaria vaccine development based on merozoite surface proteins of Plasmodium falciparum

Virander S. Chauhan, Syed Shams Yazdani and Deepak Gaur
Pages 757 - 762
http://dx.doi.org/10.4161/hv.6.9.12468
Abstract | PDF

Malaria is a global health problem and the need for a vaccine that could prevent millions of deaths annually cannot be further justified. A number of strategies have been adopted in the pursuit of making a successful malaria vaccine including the use of blood stage antigens which would primarily target the merozoite and prevent its replication through the asexual blood cycle of the parasite. In this regard, merozoite surface proteins have gained a lot of attention by the malaria vaccine fraternity for development as subunit vaccines. In spite of concentrated efforts spanning a long number of years, we are not close on producing a successful blood stage vaccine, especially one based on merozoite surface proteins (MSP). However, a recent systematic review with meta-analysis of 33 different studies has reported that antibodies against MSP proteins (MSP-1₁₉ and MSP-3) exhibit the strongest association with lower incidence of malaria and protection. Also the efficacy of an MSP based vaccine, Combination B, in significantly reducing parasite density among infected children in Papua New Guinea supports the development of MSP based malaria vaccines. In light of these developments, in this commentary, we address different aspects and concerns about MSP based vaccines – the need to develop MSP based blood stage malaria vaccines, our successes and failures from the current and past MSP vaccine trails, the lessons learnt from these studies, the future directions and challenges that still face us.




SPECIAL FEATURE

Open Access Article

Dr. John D. Clemens’acceptance speech: 2010 Albert B. Sabin Gold Medal Award

John D. Clemens
Pages 763 - 766
http://dx.doi.org/10.4161/hv.6.9.12583
Abstract | PDF

http://www.sabin.org/digital-library/video/2010-albert-b-sabin-gold-medal-acceptance-speech




LETTER

Open Access Article

Effectiveness of H1N1 vaccine against reported Influenza A (H1N1)

Chuanxi Fu
Pages 767 - 768
http://dx.doi.org/10.4161/hv.6.9.12638
PDF